There is a well established epidemiological association between the incidence of affective episodes and suicides and the seasons. Our group has previously described patients who regularly become depressed each winter, and we have called this syndrome Seasonal Affective Disorder (SAD). One approach to understanding how changes in mood are mediated by seasonal changes in this population is to study physiological and biochemical parameters at different times of the year in people whose mood is vulnerable to seasonal changes and in healthy controls. This may yield insights into the mechanism of seasonal influences on the incidence of affective episodes in the general population. We have shown that patients with SAD (nine studied so far) have significantly increased sleep length and sleep latency (the time it takes to fall asleep) but a significant decrease in slow wave (delta) sleep in the winter. These seasonal changes have not been found in healthy volunteers. Patients with SAD complain of hypoglycemia symptoms in the winter only. We are currently performing glucose tolerance tests on patients and controls in winter and summer. A marked seasonal variation in brain serotonin and platelet serotonin reuptake has been described. We collected 24-hour urine specimens and, in collaboration with Dr. Markku Linnoila, have measured serotonin and th serotonin metabolite, 5HIAA, in urine in summer and winter in eight subjects but have found no seasonal differences in these variables thus far. Future plans involve a more extensive biological work-up of patients and controls.